Asynchronous digital health interventions for reviewing asthma: A mixed-methods systematic review protocol

Introduction People living with asthma require regular reviews to address their concerns and questions, assess control, review medication, and support self-management. However, practical barriers to attending face-to-face consultations might limit routine reviews. Reviewing asthma using asynchronous digital health interventions could be convenient for patients and an efficient way of maintaining communication between patients and healthcare professionals and improving health outcomes. We, therefore, aim to conduct a mixed-methods systematic review to assess the effectiveness of reviewing asthma by asynchronous digital health interventions and explore the views of patients and healthcare professionals about the role of such interventions in delivering asthma care. Methods We will search MEDLINE, Embase, Scopus, PsycInfo, CINAHL, and Cochrane Library from 2001 to present without imposing any language restrictions. We are interested in studies of asynchronous digital health interventions used either as a single intervention or contributing to mixed modes of review. Two review authors will independently screen titles and abstracts, and retrieve potentially relevant studies for full assessment against the eligibility criteria and extract data. Disagreements will be resolved by discussion with the review team. We will use ‘Downs and Black’ checklist, ‘Critical Appraisal Skills Programme’, and ‘Mixed Methods Appraisal Tool’ to assess methodological quality of quantitative, qualitative, and mixed-methods studies respectively. After synthesising quantitative (narrative synthesis) and qualitative (thematic synthesis) data separately, we will integrate them following methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Conclusion The findings of this review will provide insights into the role of asynchronous digital health interventions in the routine care of people living with asthma. Trial registration Systematic review registration: PROSPERO registration number: CRD42022344224.


Introduction
Asthma is a common, long-term airway disease affecting up to 18% of all age groups globally [1,2]. Although, hospitalisation and deaths from asthma have declined in some countries, asthma continues to exert an unacceptably high burden on healthcare systems and society, resulting in reduced productivity at work and social disruption [2]. National and international guidelines recommend that people with asthma should be provided with self-management education reinforced by a personalised asthma action plan and supported by regular review to improve their control over their asthma [3][4][5]. An asthma review is a routine check-up of people with asthma to assess control, respond to that assessment by adjusting the management strategy, as well as to explore patients' thoughts, concerns, and expectations, and to guide selfmanagement [6,7]. Asthma reviews should be completed regularly (at least annually in stable patients) as a scheduled appointment [8]. A more frequent review may be necessary when a diagnosis is first made or for those who have poor asthma control [8]. However, across the United Kingdom (UK) National Health Service (NHS), 1 in 20 patients miss general practice (GP) appointments [9], and asthma clinics have higher than average proportion of missed appointments [10]. Practical barriers such as geographical distance, work commitments, transportation time and cost, long waiting time to attend face-to-face consultations may be barriers to regular reviews of asthma [11].
Digital health uses innovative information and communication technology to meet health demands. The term 'digital health' is an umbrella term encompassing eHealth, mHealth, health information technology, wearable devices, telehealth, telemedicine, and increasingly is linked with advanced computing such as machine learning and artificial intelligence [12,13]. The World Health Organization (WHO) in 2005 urged member states to draw up a strategic plan for promotion of equitable, affordable and universal access to the benefits of digital health services [14]. In 2012, the European health policy framework-Health 2020 highlighted the importance of digital technology in advancing public health priorities and achieving the healthrelated Sustainable Development Goals [15,16]. In the UK [17], there has been a drive over the last decade to increase the use of digital health interventions for managing and monitoring people with long-term conditions at home, and reduce the need for avoidable visits to their GP practice and hospital. For asthma, a condition that places a substantial burden on healthcare systems, using digital health interventions to review asthma could be convenient for patients and an efficient way of maintaining communication between patients and healthcare professionals and improving health outcomes [18].
Digital health interactions are typically categorised as: synchronous or real-time, a live consultation (for example, videoconferencing between patients and healthcare professionals); or asynchronous or 'store-and-forward', a non-concurrent consultation (for example, transmission of clinical data from patients through email that allows a healthcare professional to review the data and provide feedback at a later time) [19,20]. Synchronous remote asthma reviews using telephone or videoconferencing have become mainstream during the COVID-19 pandemic [21,22]. They are relatively well investigated and have been shown to increase asthma review rates without clinical disadvantage or loss of satisfaction [23][24][25][26][27]. Asynchronous reviews may overcome the temporal limitations of in-person and remote synchronous care, and have the potential to support the care of large numbers of patients with asthma [28]. Existing systematic reviews (see Table 1) have synthesised the evidence for a broad range of digital technologies, telemonitoring and telehealth (the terminology is used inconsistently) [18, [29][30][31][32][33][34][35][36][37] but there are no reviews synthesising the evidence for the effectiveness specifically of asynchronous digital health interventions for routine asthma care, nor exploring the views and experiences of patients and/or professional stakeholders on their utility. We therefore aimed to systematically review the qualitative and quantitative evidence to derive recommendations for policy and practice on the use of asynchronous digital health interventions for reviewing asthma.

Review questions
Specifically the review questions are: 1. How are asynchronous digital health interventions used for reviewing asthma?

Methodology
We will follow the methodology in the Cochrane Handbook for Systematic Reviews of Interventions to conduct this mixed-methods review [38]. We will follow a results-based convergent design where qualitative and quantitative data will be analysed and presented separately but integrated using a further synthesis [39]. The review is registered with PROSPERO (ID: CRD42022344224), any changes to the published record will be reported.

Search strategy
One review author (MNU) will develop a search strategy involving the review team (HP, VH, KM, JS and MH) and a senior librarian from the University of Edinburgh. MNU will identify records through searching the following databases: MEDLINE, Embase, Scopus, PsycInfo, CINAHL, and Cochrane Library (S1 Appendix). We will search the databases from 2001 because access to the internet increased after the introduction of third-generation (3G) cellular technologies, and interactive asynchronous communication thus became a viable option for more people [40]. We will not impose any restriction on language of publication during database searching and arrange translation to English of potentially relevant quantitative studies to enable selection and data extraction [41]. However, we will only consider qualitative and mixed-methods studies written in English because of the loss of nuance with language translation [42] but we will provide a brief description in the final results. We will conduct a pre-publication update by checking the reference lists and conducting forward citation of all studies selected for additional eligible studies [43].

Study selection
Following the search, all identified citations will be downloaded into EndNote 20 (Clarivate Analytics, PA, USA) and duplicates removed using SRA Deduplicator software [44]. Two authors (MNU and MH) will independently screen titles and abstracts, retrieve and review full-text papers for inclusion of studies against the eligibility criteria (see Table 2) using Covidence (www.covidence.org) [45]. Reasons for exclusion of full-text studies that do not meet the inclusion criteria will be recorded and reported. Any disagreements that arise between the two reviewers (MNU and MH) at any stage of the study selection process will be resolved through discussion and involve the review team (HP, VH, KM, JS) if necessary. The results of the search will be presented in a Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) flow diagram [46].

Data extraction and management
Two review authors (MNU and MH) will pilot the data extraction form on at least one quantitative and one qualitative study before data are extracted from the remaining included studies using a refined form. We will extract data into a Microsoft Word and Excel file as necessary. Two review authors (MNU and MH) will independently extract data from all included studies (quantitative, qualitative and mixed-methods) and another author (HP/VH/KM/JS) will check accuracy of data transcribed into tables or meta-analyses. Any disagreement between MNU and MH relating to data extraction will be resolved by consensus. A third review author (HP/ VH/KM/JS) will be involved to resolve any outstanding disagreement as necessary.
Quantitative studies. Two review authors (MNU and MH) will independently extract the following study characteristics from included studies.
• Participants: number, mean age, gender, severity of condition, diagnostic criteria, baseline lung function, smoking history, inclusion criteria and exclusion criteria. • Methods: study design, duration of study, number of study centres and location, study setting, and date of study.
• Outcomes: primary and secondary outcomes specified and collected: e.g., mean (standard deviation), median (interquartile range), confidence intervals, P-values, measurement scales used, and time points reported.
• Notes: funding for studies and conflicts of interest of trial authors.
Qualitative studies. Two review authors (MNU and MH) will extract the following study characteristics from included studies.
• Participants: number, mean age, gender, severity of condition, diagnostic criteria, baseline lung function, smoking history, inclusion criteria and exclusion criteria.
• Methods: sampling, setting (e.g. community or outpatient or hospital), data collection (e.g. how the authors conducted the study, length of interviews, whether interviews were recorded, use of interview guide), data analysis (e.g. method of analysis of transcripts, framework used, coding, thematic map).
• Results: themes and quotes from participants, and authors' interpretations.
Mixed-method studies. Two review authors (MNU and MH) will independently extract the study characteristics as listed above for the quantitative and qualitative components separately from included studies.

Dealing with missing data
We will use email to contact study authors for any unreported data or clarification of study methodologies. If data is still unavailable, we will analyse the available data and reflect on the significance of missing data in the discussion section.

PLOS ONE
Asynchronous digital health interventions for reviewing asthma

Methodological quality assessment
All included studies (quantitative, qualitative and mixed-methods) will be assessed for methodological quality independently and in duplicate by two review authors (MNU and MH). We will resolve any disagreements by discussion or by involving another author (HP/VH/KM/JS) if necessary. Quantitative studies. To assess the methodological quality of randomised controlled trials (RCTs), we will use the Cochrane risk of bias tool which assesses selection, performance, detection, attrition, reporting and other sources of bias enabling each study to be assigned as low; moderate; or high risk of bias [50]. We will record and tabulate a summary of the assessment with the overall judgement. For non-randomised studies, we will use the Downs and Black checklist [51]. To reflect the relative weight of the quantitative findings, we will adopt the previously published approach of summarising three attributes for each study (design, population size, quality score) when presenting data from the different studies [52].
Qualitative studies. We will assess study quality by identifying methodological strengths and limitations (i.e., rigour) of included studies using the Critical Appraisal Skills Programme Mixed-methods studies. We will use the Mixed Methods Appraisal Tool (MMAT) to assess risk of bias [55]. We will assess the risk of bias according to the following criteria: • Is there an adequate rationale for using a mixed-methods design to address the research question?
• Are the different components of the study effectively integrated to answer the research question?
• Are the outputs of the integration of qualitative and quantitative components adequately addressed?
• Are divergences and inconsistencies between quantitative and qualitative results adequately addressed?
• Do the different components of the study adhere to the quality criteria of each tradition of the methods involved?

Data synthesis
Quantitative data. Based on our initial scoping we anticipate that our included studies will have substantial clinical, methodological and statistical heterogeneity and meta-analysis may not be appropriate. If that is the case, we will do a narrative synthesis to show the major outcomes and their relationships [50], illustrating findings graphically if appropriate [56].
However, if we find sufficient number of RCTs, we will perform meta-analysis for the clinical outcomes (asthma control, acute attacks, and asthma-related quality of life). One review author (MNU) will conduct the meta-analysis using Review Manager software (RevMan 2020, V.5.4.1) and another review author (MH) will check data accuracy. We will conduct a pooled quantitative synthesis for homogeneous data from RCTs using an inverse variance method and a random-effects model in the meta-analysis. If the included RCTs use the same outcome measurement tool, we will use pooled mean differences. However, if (as expected) outcome measurement tool varies among trials, we will consider standardised mean differences.
Qualitative data. We will use thematic synthesis to combine the findings of studies that describe the views and experiences of patients and healthcare professionals on asynchronous asthma reviews. Following recognised methodology [57], two review authors (MNU and MH) will begin by familiarising themselves with the data against the aims of the review and note recurrent themes across the studies. After that they will develop a coding framework in discussion with the review team (HP, VH, KM, and JS). MNU and MH will independently perform line-by-line initial coding of the findings of the included studies (defined as all the text/quotes under the heading of 'results' or 'findings') translating the concepts from one study to another. They will then search for themes according to the predetermined thematic framework adding additional themes as they emerge. Analysis will be iterative and involve the multi-disciplinary author team before finalising the overarching themes and sub-themes. We will initially analyse patients and healthcare professionals' data separately to identify, for example, conflicting views or experiences. If we find that the views and experiences are similar, we may combine the two subgroups in subsequent syntheses. We will generate tables of author-reported categories, themes, and subthemes regarding asynchronous online asthma reviews.
Combining quantitative and qualitative data. After synthesising quantitative and qualitative data separately, we will integrate them following the methods and recommendations outlined in the Cochrane Handbook [58]. We will choose the appropriate methods and tools for integration as the review progresses following the Cochrane Qualitative and Implementation Methods Group guidance [59]. We anticipate that we will juxtapose the quantitative and qualitative findings in a matrix. The findings from the qualitative evidence synthesis (e.g. intervention components linked to acceptability or feasibility of the interventions) will drive juxtaposition, and these findings will make up one side of the matrix. The other side of the matrix will contain findings on intervention effects (e.g., improves outcome, no difference in result, unknown impacts). The presence or absence of features indicated by the hypotheses obtained from the qualitative synthesis will be used to categorise quantitative studies based on findings on intervention effects and the presence or absence of features specified by the qualitative synthesis [60]. Observed patterns in the matrix (if any) will be used to explain variations in quantitative study findings and to identify research gaps [61].
Interpretation will be aided by discussion within the multidisciplinary team and with the insights of patient and public involvement colleagues from the Asthma UK Centre for Applied Research (https://www.ed.ac.uk/usher/aukcar).

Assessment of confidence in evidence
Quantitative data. We will use the five GRADE (Grading of Recommendations Assessment, Development and Evaluation) considerations (risk of bias, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of evidence for the primary quantitative outcomes following the methods and recommendations described in the Cochrane Handbook [62]. We will use GRADEpro GDT software [63] and provide footnotes to explain any decisions to downgrade the quality of evidence. Qualitative data. We will follow the methods and recommendations of the Cochrane Qualitative and Implementation Methods Group [54] and use the Grades of Recommendation, Assessment, Development, and Evaluation-Confidence in the Evidence from Qualitative Reviews (CERQual) approach to assess confidence in synthesised qualitative findings [64]. CERQual includes four domains: methodological limitations, relevance of contributing studies to the research question, coherence of study findings, and adequacy of data supporting the study findings. We will summarise findings of the four domains for each outcome and provide justification to explain any decisions to downgrade the quality of evidence.

Dissemination
In addition to publishing in a peer-reviewed journal, we will share our review findings at national and international scientific meetings and conferences. Additionally, we will employ innovative dissemination techniques including online seminars and social media.

Discussion
Remote consultation with limited face-to-face contact is likely to become an important component of global models of asthma care. Reviewing asthma by asynchronous digital health interventions has the potential to prompt timely intervention and improve several areas of asthma management such as disease disparity, medication adherence, patient-clinician communication, supported self-management and make future asthma management more proactive. Asynchronous digital interventions for reviewing asthma are likely to be convenient, but little is known about how this technology is being used, if/how it is acceptable and useful to patients, and if it is perceived as effective and safe by the professionals in different healthcare settings across the world. The findings of this review are expected to provide valuable insight into organising routine care for people living with asthma in the context of multiple modes of consulting in a way that benefits both patients and healthcare professionals.